Genetics, Vol. 167, 559-567, June 2004, Copyright © 2004
doi:10.1534/genetics.103.021196

Epistasis and Its Relationship to Canalization in the RNA Virus {phi}6

* Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599
{dagger} Division of Biology, University of California, San Diego, California 92093

1 Corresponding author: Department of Biology, CB# 3280, University of North Carolina, Chapel Hill, NC 27599.
E-mail: cburch{at}bio.unc.edu

Although deleterious mutations are believed to play a critical role in evolution, assessing their realized effect has been difficult. A key parameter governing the effect of deleterious mutations is the nature of epistasis, the interaction between the mutations. RNA viruses should provide one of the best systems for investigating the nature of epistasis because the high mutation rate allows a thorough investigation of mutational effects and interactions. Nonetheless, previous investigations of RNA viruses by S. Crotty and co-workers and by S. F. Elena have been unable to detect a significant effect of epistasis. Here we provide evidence that positive epistasis is characteristic of deleterious mutations in the RNA bacteriophage {phi}6. We estimated the effects of deleterious mutations by performing mutation-accumulation experiments on five viral genotypes of decreasing fitness. We inferred positive epistasis because viral genotypes with low fitness were found to be less sensitive to deleterious mutations. We further examined environmental sensitivity in these genotypes and found that low-fitness genotypes were also less sensitive to environmental perturbations. Our results suggest that even random mutations impact the degree of canalization, the buffering of a phenotype against genetic and environmental perturbations. In addition, our results suggest that genetic and environmental canalization have the same developmental basis and finally that an understanding of the nature of epistasis may first require an understanding of the nature of canalization.




This article has been cited by other articles:


Home page
GeneticsHome page
H. Gao and M. W. Feldman
Complementation and Epistasis in Viral Coinfection Dynamics
Genetics, May 1, 2009; 182(1): 251 - 263.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
P.-A. Gros, H. Le Nagard, and O. Tenaillon
The Evolution of Epistasis and Its Links With Genetic Robustness, Complexity and Drift in a Phenotypic Model of Adaptation
Genetics, May 1, 2009; 182(1): 277 - 293.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
D. S. Campo, Z. Dimitrova, R. J. Mitchell, J. Lara, and Y. Khudyakov
Coordinated evolution of the hepatitis C virus
PNAS, July 15, 2008; 105(28): 9685 - 9690.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
P. Carrasco, F. de la Iglesia, and S. F. Elena
Distribution of Fitness and Virulence Effects Caused by Single-Nucleotide Substitutions in Tobacco Etch Virus
J. Virol., December 1, 2007; 81(23): 12979 - 12984.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. M. Desai, D. Weissman, and M. W. Feldman
Evolution Can Favor Antagonistic Epistasis
Genetics, October 1, 2007; 177(2): 1001 - 1010.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. T. Ferris, P. Joyce, and C. L. Burch
High Frequency of Mutations That Expand the Host Range of an RNA Virus
Genetics, June 1, 2007; 176(2): 1013 - 1022.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
F. de la Iglesia and S. F. Elena
Fitness Declines in Tobacco Etch Virus upon Serial Bottleneck Transfers
J. Virol., May 15, 2007; 81(10): 4941 - 4947.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
V. Ayme, J. Petit-Pierre, S. Souche, A. Palloix, and B. Moury
Molecular dissection of the potato virus Y VPg virulence factor reveals complex adaptations to the pvr2 resistance allelic series in pepper
J. Gen. Virol., May 1, 2007; 88(5): 1594 - 1601.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
C. L. Burch, S. Guyader, D. Samarov, and H. Shen
Experimental Estimate of the Abundance and Effects of Nearly Neutral Mutations in the RNA Virus {phi}6
Genetics, May 1, 2007; 176(1): 467 - 476.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
J. J. Bull, R. Sanjuan, and C. O. Wilke
Theory of Lethal Mutagenesis for Viruses
J. Virol., March 15, 2007; 81(6): 2930 - 2939.
[Abstract] [Full Text] [PDF]


Home page
Mol Biol EvolHome page
O. G. Pybus, A. Rambaut, R. Belshaw, R. P. Freckleton, A. J. Drummond, and E. C. Holmes
Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution
Mol. Biol. Evol., March 1, 2007; 24(3): 845 - 852.
[Abstract] [Full Text] [PDF]


Home page
Mol Biol EvolHome page
M. Parera, G. Fernandez, B. Clotet, and M. A. Martinez
HIV-1 Protease Catalytic Efficiency Effects Caused by Random Single Amino Acid Substitutions
Mol. Biol. Evol., February 1, 2007; 24(2): 382 - 387.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
U. Liberman and M. W. Feldman
Evolutionary theory for modifiers of epistasis using a general symmetric model
PNAS, December 19, 2006; 103(51): 19402 - 19406.
[Abstract] [Full Text] [PDF]


Home page
Mol Biol EvolHome page
R. Sanjuan, J. Forment, and S. F. Elena
In Silico Predicted Robustness of Viroid RNA Secondary Structures. II. Interaction between Mutation Pairs
Mol. Biol. Evol., November 1, 2006; 23(11): 2123 - 2130.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
R. Sanjuan and S. F. Elena
Epistasis correlates to genomic complexity
PNAS, September 26, 2006; 103(39): 14402 - 14405.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
T. van Opijnen, M. C. Boerlijst, and B. Berkhout
Effects of random mutations in the human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments.
J. Virol., July 1, 2006; 80(13): 6678 - 6685.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
R. Sanjuan
Quantifying antagonistic epistasis in a multifunctional RNA secondary structure of the Rous sarcoma virus
J. Gen. Virol., June 1, 2006; 87(6): 1595 - 1602.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
S. Bonhoeffer, C. Chappey, N. T. Parkin, J. M. Whitcomb, and C. J. Petropoulos
Response to Comment on "Evidence for Positive Epistasis in HIV-1"
Science, May 12, 2006; 312(5775): 848c - 848c.
[Abstract] [Full Text] [PDF]


Home page
Appl. Environ. Microbiol.Home page
J. J. Dennehy, N. A. Friedenberg, Y. W. Yang, and P. E. Turner
Bacteriophage Migration via Nematode Vectors: Host-Parasite-Consumer Interactions in Laboratory Microcosms.
Appl. Envir. Microbiol., March 1, 2006; 72(3): 1974 - 1979.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
S. F. Elena and R. Sanjuan
Adaptive Value of High Mutation Rates of RNA Viruses: Separating Causes from Consequences
J. Virol., September 15, 2005; 79(18): 11555 - 11558.
[Full Text] [PDF]


Home page
GeneticsHome page
A. Poon and L. Chao
The Rate of Compensatory Mutation in the DNA Bacteriophage {phi}X174
Genetics, July 1, 2005; 170(3): 989 - 999.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
R. Sanjuan, J. M. Cuevas, A. Moya, and S. F. Elena
Epistasis and the Adaptability of an RNA Virus
Genetics, July 1, 2005; 170(3): 1001 - 1008.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
S. Bonhoeffer, C. Chappey, N. T. Parkin, J. M. Whitcomb, and C. J. Petropoulos
Evidence for Positive Epistasis in HIV-1
Science, November 26, 2004; 306(5701): 1547 - 1550.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
R. Sanjuan, A. Moya, and S. F. Elena
The contribution of epistasis to the architecture of fitness in an RNA virus
PNAS, October 26, 2004; 101(43): 15376 - 15379.
[Abstract] [Full Text] [PDF]